The purpose of the proposed research is to test the hypothesis that herpesvirus thymidine kinase (TK), which is also a deoxycytidine kinase, can promote surval and reduce mutation frequency of cells and viruses treated with mutagens. The indicator mutatioon for viruses will be reversion to wild-type of the temperature-sensitive (ts) lesion of ts TK-HSV-1 double mutants. The indicator mutation for cells will be transition from ouabain sinsitivity to ouabain resistance. Human and mouse cells will contain either : (1) their own tk genes; (ii) no functional tk genes; (iii) a heterologous cellular tk gene; or (iv) herpesvirus tk genes. Survival and mutation frequency will be studied in cells and viruses treate separetely by various chemical and physical and physical mutagens. treated and untreated cells will then be infected with treated and untreated viruses in arious combinations, and survival and mutation frequency of viruses will be mueasured. The inducibility of survival and mutation will be assessed from results of experiments with a delay between infection and excleoside triphosphat (dNTP) pool imbalances on mutation frequency and reactivation, nucleosides will be added to the exogenous media in selected experiments to bias concentrations of available dNTPs. the results will be used to select components for the design of a sensitive system for detection of mutagenesis in cells and viruses.